Studies Widen Role of Germs in Disease
By Rick Weiss
Washington Post Staff Writer
Monday, March 1, 1999; Page A1
From gallstones to arthritis to heart disease, many
illnesses long presumed
to have roots in genes or lifestyle may be caused largely
by infectious
agents, a growing number of scientists believe. That
prospect is raising the
intriguing possibility that people can "catch" kidney
stones, cerebral palsy
or Alzheimer's disease.
Most of the evidence remains circumstantial. A microbe
may be
suspiciously present in people who have a disease, for
example, and not in
those who don't - suggesting, but not proving, causality.
But for some conditions - including heart disease, the
nation's top killer -
many scientists feel certain that microbes play at least
a contributing role
where none was suspected previously. Last week,
researchers announced
that they had discovered a molecular mechanism by which
mice can get
heart disease from a bacterium. And high-tech tests have
been picking up
previously undetectable bacterial "fingerprints" in
people with other
chronic conditions, strengthening the case that microbes
are the hidden
perpetrators in those diseases as well.
The implications of the new theory are enormous,
researchers say. Most
important, it suggests that vaccines or antibiotics may
have an
unexpectedly big role to play in the treatment of chronic
diseases that
today are treated with only modest success through
lifestyle changes, such
as exercise and improved diet.
"If an infectious agent is responsible for even a portion
of these diseases,
that could change the outlook for treatment and
prevention dramatically,"
said Barry Bloom, dean of the Harvard School of Public
Health. "I see
chronic disease as the next frontier for vaccines."
Bloom and others cautioned against placing too much blame
on bacteria.
For most chronic diseases, they are probably just part of
the puzzle, they
said. And the prospect of widespread, long-term use of
powerful
antibiotics carries its own problems, including the
possible emergence of
drug-resistant "superbugs." Attractive though the idea
may be, a pill or
shot will not likely allow people to ignore everything
they have learned
about how to remain healthy into old age.
"The bacteria by themselves are not going to give us the
only useful
answers," said Janice Kiecolt-Glaser of Ohio State
University, who
studies the effects of stress on health. "You could have
the bug, and if
resistance is altered by stress or other factors, you
could be more prone
to not healing or to the infection progressing."
Nonetheless, said Anne Schuchat, chief of the respiratory
diseases branch
at the Centers for Disease Control and Prevention (CDC)
in Atlanta,
chronic conditions such as heart disease take such a big
toll on society that
even a modest contribution by bacteria deserves to be
targeted. "Even if
there are still a lot of questions," she said, "it's
really worth a lot of
attention."
The revolution began about five years ago, when
definitive evidence arose
that stomach ulcers are caused not by excess stomach
acid, as had long
been presumed, but by the bacterium Helicobacter pylori.
It wasn't easy persuading the scientific community to
accept the new
model. Barry Marshall, an Australian scientist with a
flair for theatrics,
resorted to swallowing a beaker of the bacteria to help
settle the question.
Today, ulcers are treated primarily with antibiotics
instead of
acid-blocking drugs.
Infectious disease specialists now are turning their
attention to coronary
artery disease, which is caused by a progressive buildup
of fatty deposits
inside vessels that feed the heart. Scientists have long
known that diabetes,
high blood pressure, tobacco use and a family history of
the disease
increase a person's odds of artery disease and the risk
of a subsequent
heart attack or stroke. But those factors account for
only about half the
incidence of this disease.
Several lines of research support the proposition that a
microbe might
cause coronary artery disease. In 1997, Boston
researchers showed that
men with higher levels of a certain protein circulating
in their blood over a
period of years had an increased risk of eventually
suffering a heart attack
or stroke. The protein is a well-known sign of
inflammation, which can
indicate a bacterial infection.
Separately, Joseph B. Muhlestein of the LDS Hospital in
Salt Lake City
and his colleagues discovered that a peculiar bacterium,
Chlamydia
pneumoniae, often can be found inside blood vessel cells
of people with
heart disease - but not generally in the cells of healthy
people.
C. pneumoniae - a close cousin of C. trachomatis, which
causes a
common sexually transmitted disease - is best known as a
cause of
pneumonia and bronchitis. It is unlike most other
bacteria because it lives
not on cells but inside them, much as a virus does.
It is possible that the microbe is just an innocent
bystander - a bacterium
that feels at home in arteries damaged by years of
hamburger consumption
and a lack of exercise. But rabbits on fatty diets
develop hardening of the
arteries much faster when they are infected with C.
pneumoniae,
suggesting that the microbes actively contribute to the
disease.
A study published in the journal Science last Friday
offered the best
evidence yet for precisely how chlamydia may cause heart
disease. A
protein found on chlamydia, it turns out, is almost
identical to one found in
heart tissue in mammals. Scientists discovered that when
a mouse's
immune system attacks the bug, it accidentally attacks
the heart protein,
too. The resulting syndrome is not exactly the same as
human heart
disease, said Josef M. Penninger, the University of
Toronto immunologist
who led the study. But the similarities have convinced
him that something
very much like this may be causing heart disease in
people.
If Penninger is right, then heart disease might be
prevented or even
reversed by a drug that tempered the immune system's
reaction to
chlamydia. Scientists trying to create a vaccine against
chlamydia would
face a challenge, however. Vaccines work by stimulating
the immune
system and could inadvertently trigger the immune
response that causes
heart disease.
If the microbe, and not the immune response against it,
causes heart
disease directly then antibiotics might prove useful. Two
studies in people
have indicated that a short course of antibiotics known
to kill chlamydia
can reduce the risk of a heart attack or stroke for up to
18 months.
Another study was unable to verify the benefit and other
studies are
ongoing.
Heart disease is not the only chronic disease in which C.
pneumoniae may
play a role. Neuroscientist Brian Balin of the
Philadelphia College of
Osteopathic Medicine and his colleagues have found signs
of the microbe
in 27 of 29 autopsied brains of people with Alzheimer's
disease, but in
only one of 19 brains from non-Alzheimer's patients.
The bacteria, found in so-called glial cells that
surround neurons, may be
"opportunists" taking advantage of dying brains, Balin
said. But studies
indicate that they can cause Alzheimer-like damage. "I
think it's definitely
an agent that has to be considered as a potential
causative or at least a
risk factor for Alzheimer's disease," he said.
Gallstones and kidney stones recently have been added to
the list of
diseases that might have microbiological roots. Studies
led by Phillip B.
Hylemon of the Medical College of Virginia in Richmond,
for example,
showed that gallstone patients have 100- to 1,000-fold
higher levels of
Clostridia and eubacteria in their intestines. Those
bacteria generate
deoxycholic acid, which prompts the liver to secrete bile
especially rich in
cholesterol - a key risk factor for gallstone formation.
In one encouraging
finding, antibiotics have been shown to lower the
concentration of these
bacteria in people and decrease bile levels to below the
threshold needed
to make gallstones.
Last summer, Finnish researchers reported provocative
evidence that
"nanobacteria" - smaller than many viruses - may be a
cause of kidney
stones. Using genetic fingerprinting tests and other
methods, they found
that the bacteria can build a mineralized coating around
themselves, upon
which additional proteins and minerals can accumulate. In
one study of 30
kidney stones, all had traces of nanobacteria in their
cores. DNA studies
suggest that the nanobacteria are related to a small,
slow-growing,
rod-shaped bacteria known to cause abortions in animals
and blood
poisoning in people.
Juvenile rheumatoid arthritis, generally considered an
immune system
disorder, also may be caused by a microbe, although the
evidence remains
indirect. The proposed culprit is Mycoplasma pneumoniae,
a common
cause of "atypical pneumonia" in people. In a 17-year
Canadian study,
diagnoses of the disease peaked in the same years as M.
pneumoniae
infections did.
Some researchers suspect that scleroderma, a painful
chronic disease
affecting connective tissues under the skin, also may be
caused by
mycoplasma. A recent U.S. study found a virtually
complete
disappearance of symptoms in four of six patients treated
for one year
with an anti-mycoplasma antibiotic called minocycline.
Cerebral palsy, too, may prove to be infectious. That
disease, which
affects about 500,000 Americans and is characterized by
brain damage at
birth, was long believed to have been caused by oxygen
deprivation
before or during birth. But a study last year suggested
that infected
amniotic fluid may often be to blame.
Researchers have not isolated a particular microbe from
newborns with
cerebral palsy. But a technique being studied by David
Relman at
Stanford University may help scientists find the cause of
that and other
diseases for which there is evidence of infection but no
isolated microbe.
Relman is using DNA fingerprinting methods to find tiny
fragments of
microbial DNA in cells of people with various diseases.
Some scientists suspect that such tests will reveal
infectious causes for
more and more chronic diseases. "They will pop up in all
kinds of places,"
the University of Toronto's Penninger said.
Attractive as the emerging evidence is, not everyone is
so sure. To a
microbiologist, the world can sometimes seem full of
"infectious agents in
search of a disease," said Schuchat of the CDC. "How much
is real and
how much is a fad remains to be seen."
© Copyright 1999 The Washington Post Company